Immunoregulatory agents are substances that regulate or modify the normal or aberrant immune response of a host animal. Such agents are extremely important in medical applications, specifically in diseases that are caused by an abnormal immune response, such as rheumatoid arthritis (RA), systemic lupus erythrematosis (SLE), AIDS, etc. They are also useful where it is desirable to suppress normal immune response, such as in organ transplants and other types of tissue or organ grafts.
Various immunoregulatory agents are known in the art, but all have significant disadvantages. Some examples are cyclophosphamide, methotrexate, 6-MP and cyclosporin A. These drugs suffer from various shortcomings such as toxic side effects and a narrow therapeutic index that severely limits their therapeutic application.
Immune response can be modified in many ways. One of the most desirable approaches is to influence or modulate the activity of suppressor T-cells. Suppressor T-cells are an important class of lymphocyte that have an important role in the regulation of immune response. These cells play an important role in the development of immuno-tolerance. Malfunction of these cells is believed to play a role in the pathogenesis of auto-immune diseases, such as RA and SLE. These diseases are believed to be caused by diminished suppressor T-cell activity and a resultant overproduction of auto-antibodies. This situation may be reversed by activation of suppressor T-cells. In organ transplants, activation of suppressor T-cells, with the consequential suppression of the immune response, helps promote tolerance and prevent rejection of transplanted organs to the recipient's immune system.
Therefore, it would be extremely advantageous to have an immunoregulatory agent that activates suppressor T-cells, thereby regulating immune response, but which has a wide therapeutic index and does not have toxic side effects at physiological doses. The present invention satisfies this need and provides other related advantages.